This proposal represents a request for continued funding of the NIH-sponsored Clinical Pharmacology Fellowship Training Program at the Mayo Clinic-Mayo Clinic College of Medicine-Mayo Medical School. This research training experience is integrated within a broad curriculum that exposes Trainees to critical aspects of the science underlying Clinical Pharmacology ~ all within a supportive, mentoring environment. Clinical Pharmacology represents a "bridge discipline" that is devoted to the study of the interaction between humans and drugs. Within the context of the ongoing" revolution" that is occurring in biomedical science, a revolution that promises to transform medical practice, Clinical Pharmacology lies at the confluence of the disciplines of molecular pharmacology, genomics, proteomics, bioinformatics and rational therapeutics - with an ultimate goal of scientifically "individualized" drug therapy. Therefore, Clinical Pharmacology seeks to enhance our understanding of the molecular basis for drug response and to apply that information at the translational interface to make it possible to tailor drug therapy to both the underlying disease process and the unique characteristics of each individual patient. However, our ability to take advantage of this unique opportunity will require that we train a new generation of Clinical Pharmacologists in science that is based on a foundation provided by the "new biology". Large, comprehensive, integrated academic medical centers like the Mayo Clinic are ideally positioned to train this new generation of Clinical Pharmacologists. Mayo is able to do that because of its long history of integrating basic and clinical medical research, because of a long tradition of contributing to the discipline of Clinical Pharmacology, because the Mayo Clinical Pharmacology Training Program has had decades of experience in successfully recruiting and training physician scientists and because of an historical focus at Mayo on translational science. The Mayo Clinical Pharmacology Fellowship Training Program will continue to emphasize strong laboratory-based research training, systematic exposure to clinical science, and a structured mentorship - with the goal of preparing each Fellow to become a future leader in Clinical Pharmacology.